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Immuno Nutrition by L-citrulline for Critically Ill Patients

Not Applicable
Completed
Conditions
Intubation
Pulmonary Ventilation
Interventions
Procedure: Enteral nutrition
Dietary Supplement: Placebo
Dietary Supplement: L-Citrulline
Registration Number
NCT02864017
Lead Sponsor
Rennes University Hospital
Brief Summary

The main objective of this study is to demonstrate that the only administration of L-citrulline, can improve immune functions in critically ill patients at high risk of nosocomial infection.

Detailed Description

This is a multicentric therapeutic trial, randomized and double blind: standard enteral nutrition plus L-citrulline (5 grams/12 Hours for 5 days from the admission in Intensive Care Unit (ICU)) versus standard enteral nutrition plus placebo.

Methods-Patients: Non-surgical patients admitted in medical intensive care unit, under mechanical ventilation for an expected duration \> 2 days, without severe sepsis or septic shock, will be enrolled. Symptoms leading for ICU admission ongoing for five days maximum. On admission (before treatment), the severity will be evaluated with the Sepsis-related Organ Failure Assessment (SOFA) score together with an assessment of plasmatic arginine, cytokines (InterLeukin-6 (IL6) ), and expression of Human Leukocyte Antigen - antigen D Related (HLA-DR) by monocytes. The same evaluation will be repeated on day 3 (during treatment) and on day 7 (after treatment).

The enrolment of 100 patients is statistically enough to demonstrate a decreased SOFA scores in the L-citrulline group as compared to the placebo group on day 7.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
120
Inclusion Criteria
  • age > 18 years
  • medical patient (absence of recent surgery or trauma)
  • initial aggression < 5 days
  • mechanically ventilated with expected duration of mechanical ventilation > 2 days
  • exclusive enteral nutrition
  • absence of previous immunosuppression
Exclusion Criteria
  • severe sepsis
  • septic shock
  • obesity defined as BMI above 40
  • pregnancy

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Control groupEnteral nutritionEnteral nutrition 5-day placebo treatment
Control groupPlaceboEnteral nutrition 5-day placebo treatment
L-Citrulline groupEnteral nutritionEnteral nutrition 5-day L-citrulline treatment (10 grams/day)
L-Citrulline groupL-CitrullineEnteral nutrition 5-day L-citrulline treatment (10 grams/day)
Primary Outcome Measures
NameTimeMethod
Organ failure score comparison D7At day 7

Organ failure score (SOFA score) on day 7 in the L-citrulline group as compared to the placebo group

Secondary Outcome Measures
NameTimeMethod
Organ failure score comparison D3At day 3

Organ failure score (SOFA score) on day 3 in the L-citrulline group as compared to the placebo group

Plasmatic concentration of IL6At day 7

Comparison of the plasmatic concentration of interleukin-6 between the L-citrulline group and the placebo group

Mortalityduring the stay in hospital, up to 28 days

* Mortality in intensive care and in hospital : Comparison between the L-citrulline group and the placebo group

* Duration of mechanical ventilation.

SOFA score evolution between randomisation and D7up to 7 days

Binary criterion of success or failure :

- Success is defined by: an improved SOFA score of at least 2 points from randomization to Day 7 or an improvement in the general condition yielding the release of the unit;

- Failure is defined by an improved SOFA score but less than 2 points, no improvement or worsening of the SOFA score from randomization to Day 7 or the patient's death before J7;

Plasmatic concentration of L-arginineAt day 7

Comparison of the plasmatic concentration of L-arginine and its metabolites between the L-citrulline group and the placebo group

Incidence of nosocomial infectionsduring the stay in the ICU, an average of 7 days

Comparison between the L-citrulline group and the placebo group

Duration of mechanical ventilationduring the stay in ICU, an average of 7 days

Duration of mechanical ventilation: Comparison between the L-citrulline group and the placebo group

Expression of HLA-DRAt day 7

Expression of HLA-DR in the L-citrulline group as compared to the placebo group

HLA-DRAt day 7

Comparison of the percentage of expression of monocytic HLA-DR between the L-citrulline group and the placebo group

Length of stayduring the stay in hospital, up to 28 days

Length of stay in ICU and hospital: Comparison between the L-citrulline group and the placebo group

Trial Locations

Locations (4)

CHU Nantes

🇫🇷

Nantes, France

Paris - HEGP

🇫🇷

Paris, France

CHU Angers

🇫🇷

Angers, France

Rennes Hospital University

🇫🇷

Rennes, France

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